In this study, we fabricated and characterized a smart shear-thinning hydrogel composed of gelatin and laponite for localized drug delivery. We added chitosan (Chi) and poly N-isopropylacrylamide-co-Acrylic acid (PNIPAM) particles to the shear-thinning gel to render it pH-responsive. The effects of total solid weight and the percentage of laponite in a solid mass on the rheological behavior and mechanical properties were investigated to obtain the optimum formulation. The nanocomposite gel and particles were characterized using Fourier-transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), zeta potential, and dynamic light scattering techniques. Finally, release related experiment including degradability, swelling and Rhodamine B (Rd) release at various pH were performed. The results suggest that incorporation of silicate nanoplatelets in the gelatin led to the formation of the tunable porous composite, with a microstructure that was affected by introducing particles. Besides, the optimum formulation possessed shear-thinning properties with modified rheological and mechanical properties which preserved its mechanical properties while incubated in physiological conditions. The release related experiments showed that the shear-thinning materials offer pH-sensitive behavior so that the highest swelling ratio, degradation rate, and Rd release were obtained at pH 9.18. Therefore, this nanocomposite gel can be potentially used to develop pH-sensitive systems.

Wound infection is a major clinical challenge that can significantly delay the healing process, can create pain, and requires prolonged hospital stays. Pre-clinical research to evaluate new drugs normally involves animals. However, ethical concerns, cost, and the challenges associated with interspecies variation remain major obstacles. Tissue engineering enables the development of in vitro human skin models for drug testing. However, existing engineered skin models are representative of healthy human skin and its normal functions. This paper presents a functional infected epidermis model that consists of a multilayer epidermis structure formed at an air-liquid interface on a hydrogel matrix and a three-dimensionally (3D) printed vascular-like network. The function of the engineered epidermis is evaluated by the expression of the terminal differentiation marker, filaggrin, and the barrier function of the epidermis model using the electrical resistance and permeability across the epidermal layer. The results showed that the multilayer structure enhances the electrical resistance by 40% and decreased the drug permeation by 16.9% in the epidermis model compared to the monolayer cell culture on gelatin. We infect the model with Escherichia coli to study the inflammatory response of keratinocytes by measuring the expression level of pro-inflammatory cytokines (interleukin 1 beta and tumor necrosis factor alpha). After 24 h of exposure to Escherichia coli, the level of IL-1β and TNF-α in control samples were 125 ± 78 and 920 ± 187 pg/mL respectively, while in infected samples, they were 1429 ± 101 and 2155.5 ± 279 pg/mL respectively. However, in ciprofloxacin-treated samples the levels of IL-1β and TNF-α without significant difference with respect to the control reached to 246 ± 87 and 1141.5 ± 97 pg/mL respectively. The robust fabrication procedure and functionality of this model suggest that the model has great potential for modeling wound infections and drug testing.